1. Field of the Invention
The present invention relates to new substituted 2-acylamino-2-deoxy-glucono-1,5-lactone type compounds, to compositions containing said compounds that are surfactants and/or biologically active compounds, to methods for producing said compounds and to intermediates in their production.
2. Prior Art
Examples of glycosylated surfactants comprising a lactone function have been cited in the literature. Pocalyko et al., (1996) (5) and Kwoh et al. (1995) (3) describe the enzymatic synthesis of 6xe2x80x94O-dodecyl gluconolactone, while Kida et al. (1994) (1) use the lactone function to synthesise surfactants that are degradable in an acidic medium.
However, such lactones do not contain an N-acyl moiety or an N-acetylglucosamine moiety; this moiety is important in the recognition of certain enzymes.
Examples of the synthesis of N-acetyl glucosaminidase inhibitors have been cited in the literature by Pokorny et al., (1974) (6); Wolk et al. (1992) (7); Knapp et al. (1996) (2); and Panday et al. (1998) (4). These inhibitors exhibit major disadvantages; in particular, their low dissociation constant (between 0.13 and 0.45 xcexcM) makes these potent inhibitors useless as regards affinity separation, as recovering the enzyme requires operating conditions that could cause them to denature. None of the molecules concerned has surfactant properties, in particular 2-acetamido-2-deoxy-glucono-1,5-lactone (Pokorny et al., 1974). As a result, their purely hydrophilic nature does not enable them to interact with biological membranes with a view to possible cellular penetration or disruption, or with amphiphilic compounds organised into micelles or liposomes with a view to vectorising or to liquid/liquid separation.
We have now developed a new class of substituted 2-acylamino-2-deoxy-glucono-1,5-lactone type compounds that may have the advantage of having surfactant or biodegradability properties and may be biologically active.
The present invention provides compounds with formula (I): 
where A represents R1 or xe2x80x94C(O)R1, where R1 represents a linear or branched, saturated or unsaturated alkyl group containing 1 to 30 carbon atoms, which may be partially or completely substituted by xe2x80x94Hal where Hal signifies xe2x80x94Cl, xe2x80x94Br, xe2x80x94I or xe2x80x94F, and which may be interrupted by one or more moieties selected from xe2x80x94O, xe2x80x94Sxe2x80x94, xe2x80x94C(O)xe2x80x94, xe2x80x94NR3C(O)xe2x80x94, xe2x80x94Ph(R4)n xe2x80x94, and xe2x80x94CH2xe2x80x94CH2xe2x80x94O)nxe2x80x2xe2x80x94, where R3 represents xe2x80x94H or xe2x80x94CH2)nxe2x80x3xe2x80x94CH3 where nxe2x80x3 is 0 to 17; R4 represents xe2x80x94H, xe2x80x94CH3, xe2x80x94C2H5, xe2x80x94C3H7 and n is 0 to 4 and nxe2x80x2 is 1, 2 or 3, or R1 represents a cyclane radical with a diterpene or triterpene root; and R2 represents a linear or branched C1 to C11 alkyl group.
The compounds of the invention have the advantages of glycosylated glucosamine-based surfactants such as biodegradability.
Further, some of these compounds may have antimicrobial and antifungal properties. Finally, these compounds may be useful in enzymatic inhibition or enzyme recognition methods.
The invention al so concerns methods for preparing compounds with the above formula I. These methods comprise at least the following steps:
a) acylating glucosamine hydrochloride using an acid chloride with formula R2C(O)Cl;
b) protecting the C1 hydroxyl group by a P1 group, and the C3 and C4 hydroxyl group by groups P2 and the C6 hydroxyl group;
c) deprotecting the protected C6 hydroxyl group;
d) 6xe2x80x94O-acylation with a compound with formula R1C(O)Cl or 6xe2x80x94-alkylation with a compound with formula R1Hal to obtain the compound with formula: 
e) deprotecting the protected C1 hydroxyl group to obtain the compound with formula: 
f) oxidising the compound obtained at e) to obtain the compound with formula: 
g) deprotecting the protected C3 and C4 hydroxyl groups of the compound obtained in f) to obtain the compound with formula I;
where A, R2 and Hal have the same meanings as those given above, and P1 and P2 are protective groups.
In a further aspect, the invention concerns, as intermediate compounds, compounds with the following formulae: 
where A, R2, P1 and P2 have the meanings given above.
Further, the present invention concerns compositions comprising at least one or more compounds of the invention, one or more compounds obtained by the method of the invention or intermediate products in said method.
Finally, the invention concerns compounds with formula I as surfacts or compounds for use in an enzymatic inhibition method or an enzyme recognition method.
The present invention will be better understood from detailed description and examples below and from the accompanying figures.